title: Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity.
abstract: The membrane-associated guanylate kinases (MAGUKs) PSD-95, PSD-93 and SAP102 are thought to have crucial roles in both AMPA receptor trafficking and formation of NMDA receptor-associated signalling complexes involved in synaptic plasticity. While PSD-95, PSD-93, and SAP102 appear to have similar roles in AMPA receptor trafficking, it is not known whether these MAGUKs also have functionally similar roles in synaptic plasticity. To explore this issue we examined several properties of basal synaptic transmission in the hippocampal CA1 region of PSD-93 and PSD-95 mutant mice and compared the ability of a number of different synaptic stimulation protocols to induce long-term potentiation (LTP) and long-term depression (LTD) in these mutants. We find that while both AMPA and NMDA receptor-mediated synaptic transmission are normal in PSD-93 mutants, PSD-95 mutant mice exhibit clear deficits in AMPA receptor-mediated transmission. Moreover, in contrast to the facilitation of LTP induction and disruption of LTD observed in PSD-95 mutant mice, PSD-93 mutant mice exhibit deficits in LTP and normal LTD. Our results suggest that PSD-95 has a unique role in AMPA receptor trafficking at excitatory synapses in the hippocampus of adult mice and indicate that PSD-93 and PSD-95 have essentially opposite roles in LTP, perhaps because these MAGUKs form distinct NMDA receptor signalling complexes that differentially regulate the induction of LTP by different patterns of synaptic activity.
authors.affiliation: Department of Physiology, David Geffen School of Medicine at UCLA, 53-231 Center for the Health Sciences, Box 951751, Los Angeles, CA 90095-1751, USA.
authors.forename: Holly J
authors.initials: HJ
authors.lastname: Carlisle
authors.forename: Ann E
authors.initials: AE
authors.lastname: Fink
authors.forename: Seth G N
authors.initials: SG
authors.lastname: Grant
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: O'Dell
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D026941:Sodium Channel Blockers; C012647:QX-314; D008012:Lidocaine; C501445:Dlg2 protein, mouse; D051528:Guanylate Kinases